Abstract
CPT-11, a semi-synthetic derivative of camptothecin, was investigated for its activity in panels of 15 human ovarian- cancer lines and 10 human soft-tissue sarcoma lines grown s.c. in nude mice. Various factors were analyzed that may be of influence on the extent of tumor-growth inhibition induced by CPT-11. At equitoxic doses, CPT-11 was more effective in the daily ×5 schedule than the weekly ×2 schedule, although a 2-fold higher dose was administered in the weekly ×2 schedule. Since i.p. and i.v. injections were similarly effective, the selected treatment schedule was 20 mg/kg i.p. daily ×5, starting when tumors measured approximately 150 mm3. Growth inhibition of ≥75% was obtained in 8/15 human ovarian-cancer lines and in 6/10 human soft-tissue sarcoma lines. A weak correlation was found between topoisomerase-1 mRNA in xenograft tissues and sensitivity to CPT-11. Relative topoisomerase-1 expression was highest in MRI-H-207 and WLS-160 xenografts, in which CPT-11 was able to induce cures of all tumors. The high efficacy in the 2 panels of human tumor lines suggests over-prediction of its potential clinical activity in these tumor types. The difference in efficacy of CPT-11 between species may be related to the metabolism of the drug, since CPT-11 is converted more efficiently into SN-38 in mice. In addition, mice may be less sensitive to SN-38-induced side-effects. On the basis of the preclinical data, frequent administration of lower doses of CPT-11 should be considered in order to increase response rates in the clinic.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 891-896 |
| Number of pages | 6 |
| Journal | International Journal of Cancer |
| Volume | 73 |
| Issue number | 6 |
| State | Published - Dec 10 1997 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Anti-tumor activity of CPT-11 in experimental human ovarian cancer and human soft-tissue sarcoma. / Jansen, Willy J M; Kolfschoten, Geertruida M.; Erkelens, Caroline A M; Van Ark-Otte, Jannette; Pinedo, Herbert M.; Boven, Epie.
In: International Journal of Cancer, Vol. 73, No. 6, 10.12.1997, p. 891-896.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anti-tumor activity of CPT-11 in experimental human ovarian cancer and human soft-tissue sarcoma
AU - Jansen, Willy J M
AU - Kolfschoten, Geertruida M.
AU - Erkelens, Caroline A M
AU - Van Ark-Otte, Jannette
AU - Pinedo, Herbert M.
AU - Boven, Epie
PY - 1997/12/10
Y1 - 1997/12/10
N2 - CPT-11, a semi-synthetic derivative of camptothecin, was investigated for its activity in panels of 15 human ovarian- cancer lines and 10 human soft-tissue sarcoma lines grown s.c. in nude mice. Various factors were analyzed that may be of influence on the extent of tumor-growth inhibition induced by CPT-11. At equitoxic doses, CPT-11 was more effective in the daily ×5 schedule than the weekly ×2 schedule, although a 2-fold higher dose was administered in the weekly ×2 schedule. Since i.p. and i.v. injections were similarly effective, the selected treatment schedule was 20 mg/kg i.p. daily ×5, starting when tumors measured approximately 150 mm3. Growth inhibition of ≥75% was obtained in 8/15 human ovarian-cancer lines and in 6/10 human soft-tissue sarcoma lines. A weak correlation was found between topoisomerase-1 mRNA in xenograft tissues and sensitivity to CPT-11. Relative topoisomerase-1 expression was highest in MRI-H-207 and WLS-160 xenografts, in which CPT-11 was able to induce cures of all tumors. The high efficacy in the 2 panels of human tumor lines suggests over-prediction of its potential clinical activity in these tumor types. The difference in efficacy of CPT-11 between species may be related to the metabolism of the drug, since CPT-11 is converted more efficiently into SN-38 in mice. In addition, mice may be less sensitive to SN-38-induced side-effects. On the basis of the preclinical data, frequent administration of lower doses of CPT-11 should be considered in order to increase response rates in the clinic.
AB - CPT-11, a semi-synthetic derivative of camptothecin, was investigated for its activity in panels of 15 human ovarian- cancer lines and 10 human soft-tissue sarcoma lines grown s.c. in nude mice. Various factors were analyzed that may be of influence on the extent of tumor-growth inhibition induced by CPT-11. At equitoxic doses, CPT-11 was more effective in the daily ×5 schedule than the weekly ×2 schedule, although a 2-fold higher dose was administered in the weekly ×2 schedule. Since i.p. and i.v. injections were similarly effective, the selected treatment schedule was 20 mg/kg i.p. daily ×5, starting when tumors measured approximately 150 mm3. Growth inhibition of ≥75% was obtained in 8/15 human ovarian-cancer lines and in 6/10 human soft-tissue sarcoma lines. A weak correlation was found between topoisomerase-1 mRNA in xenograft tissues and sensitivity to CPT-11. Relative topoisomerase-1 expression was highest in MRI-H-207 and WLS-160 xenografts, in which CPT-11 was able to induce cures of all tumors. The high efficacy in the 2 panels of human tumor lines suggests over-prediction of its potential clinical activity in these tumor types. The difference in efficacy of CPT-11 between species may be related to the metabolism of the drug, since CPT-11 is converted more efficiently into SN-38 in mice. In addition, mice may be less sensitive to SN-38-induced side-effects. On the basis of the preclinical data, frequent administration of lower doses of CPT-11 should be considered in order to increase response rates in the clinic.
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UR - http://www.scopus.com/inward/citedby.url?scp=0031564110&partnerID=8YFLogxK
M3 - Article
C2 - 9399672
AN - SCOPUS:0031564110
VL - 73
SP - 891
EP - 896
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 6
ER -